Animal model of chronic thromboembolic pulmonary hypertension by cells proliferating within pulmonary arteries

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K19444
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Respiratory organ internal medicine
• Research Institution: Chiba University
• Principal Investigator: Takayuki Jujo 千葉大学, 大学院医学研究院, 特任助教 (90736422)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: 肺高血圧症 / 肺塞栓症 / 肺動脈内膜肉腫

Outline of Final Research Achievements

Establishing an animal model of chronic thromboembolic pulmonary hypertension (CTEPH) was not successful.We injected intravenously sarcoma-like cells (SCLs cellls), myofibroblast cells to SCID mice or F344 rats. However, those cells did not proliferated. We established a cell line of pulmonary intimal sarcoma during the studying period. The cells have the requirement of malignant cells including tumorgenesis in rats. The cells highly expressed tyrosine kinase receptors (TKRs) including platelete-derived growth factor and vascular endothelial growth factor receptors (PDGFR and VEGFR). Pazopanib, which is a tyrosine kinase inhibitor (TKIs), could inhibit the proliferation of PIS-1 cells and the growth of subcutaneous tumor in rats. It was suggested that TKRs might be an treatment target for pulmonary intimal sarcoma.

Free Research Field

肺高血圧症

Academic Significance and Societal Importance of the Research Achievements

肺動脈内膜肉腫細胞では血小板由来増殖因子受容体(PDGFR)や血管内皮細胞増殖因子受容体(VEGFR)などが高発現し、これらを阻害するチロシンキナーゼ受容体阻害薬であるPazopanibがこの細胞の増殖や腫瘍増大を抑制することを発見した。本来の目的を離れた副次的な産物であるが、本研究の成果はこうした肺動脈原発腫瘍の今後の治療進歩に寄与しうるものであると考える。